Description
Efficacy of hepatitis C virus (HCV) infection treatment with interferon-free, direct-acting antivirals (DAA)-based combination therapies can be reduced by pre-existed or emerged mutation in HCV genome. The aim of the study is to analyse HCV resistance-associated substitutions (RASs) in patients’ failed therapy with combination of DAAs.. Overall 44 patients after virological treatment failure were included in study: 30 men,14 women, median age 58 years,15/44-with HIV-1 coinfection. Median HCV viral load was 5.1 E5IU/ml, HCV genotypes distribution was as follows:GT1a-6/44,GT1b-18/44,GT3a-16/44, GT2-2/44,GT4-2/44. For HCV variants resistant to NS3 Protease inhibitors, NS5A Phosphoprotease inhibitors and NS5B Polymerase inhibitors detection, HCV RNA isolation from plasma, amplification of three corresponding HCV genome regions, next-generation sequencing (Deep Cheek® HCV ABL kits, Illumina Iseq100 analyser) was performed. RASs were determined according to Geno2Pheno 0.92 virologic tool, with 15% cutoff.. Significantly, DAAs susceptibility reduced RASs, were detected in 34 of 44 patients (77%). Most often NS5A RASs were detected (28/44, 64%),followed by NS3 RASs (20/44, 45%) and NS5B (6/44, 14%). From NS5A RASs-Y93H (18/28), L31M (12/28), A30K (5/28), Q30R (4/28) were present. Detected NS3 RASs were as follows:N174S (5/20),Y56F/H (6/20),D168V/A/T (6/20). Detected NS5B were S556G (3/6), L159F(3/6),M414I(1/6). According to Geno2Pheno interpretation, Ns5A RASs lead to full resistance to one or more drugs in 27/44 patients, to intermediate (reduced) resistance in 1/44 patients. NS3 RASs lead to full or intermediate HCV resistance in10/44 and10/44 patients respectively; NS5B in 4/44 and 2/44 patients respectively.. Analysis has shown different mutations in specifically analysed HCV genes (NS3, NS5A and NS5B) in 77% patients with DAAs treatment failure in history. Most often clinically significant HCV NS5A RASs were found (28/44, 64%). These mutations can persist for >1 years after treatment discontinuation and affect the results of re-treatment. HCV genotyping for RASs detection can be used as a tool for optimal DAAs regimen choosing.
Period | 27 Mar 2023 → 31 Mar 2023 |
---|---|
Event title | RSU Research Week 2023: Research Week 2023 Rīga Stradiņš University |
Event type | Conference |
Organiser | Riga Stradins University |
Location | Riga, LatviaShow on map |
Degree of Recognition | International |